Preparation and characterization of scleroglucan drug delivery films: The effect of freeze‐thaw cycling

This study examined the effect of the freeze‐thaw process on the physical properties of films prepared from scleroglucan (Scl) hydrogels, suitable for drug delivery applications. Films made from Scl, using glycerol as plasticizer, were prepared from hydrogels by two procedures: a room temperature drying (RTD) method and a freeze‐thaw cyclic process, before the application of RTD, which results in a reinforced physically cross‐linked network. Films were characterized by studies of water vapor transmission (WVT), swelling, tensile tests, ESEM microscopy, FTIR, and drug release measurements. These determinations showed significant differences between films obtained by both treatments. The films prepared through freeze‐thaw cycles showed an important increase of the tensile strength with respect to those corresponding to films only air dried and a decreasing swelling degree in direct relationship to the number of freeze‐thaw cycles. A model drug, Theophylline, was included in these biocompatible films for in vitro drug release measurements, using a flat Franz cell. The physical differences observed between Scl films prepared with both methods can be explained proposing that the number of crosslinking points by hydrogen bonding increase when increasing the number of freezing and thawing cycles used for film preparation. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Phase decomposition upon alteration of radiation-damaged monazite-(ce) from moss, Østfold, norway

The internal textures of crystals of moderately radiation-damaged monazite-(Ce) from Moss, Norway, indicate heavy, secondary chemical alteration. In fact, the cm-sized specimens are no longer mono-mineral monazite but rather a composite consisting of monazite-(Ce) and apatite pervaded by several generations of fractures filled with sulphides and a phase rich in Th, Y, and Si. This composite is virtually a 'pseudomorph' after primary euhedral monazite crystals whose faces are still well preserved. The chemical alteration has resulted in major reworking and decomposition of the primary crystals, with potentially uncontrolled elemental changes, including extensive release of Th from the primary monazite and local redeposition of radionuclides in fracture fillings. This seems to question the general alteration-resistance of orthophosphate phases in a low-temperature, 'wet' environment, and hence their suitability as potential host ceramics for the long-term immobilisation of radioactive waste.     

Effect of laser microcutting on thermo-mechanical properties of NiTiCu shape memory alloy

The machining of shape memory alloys (SMAs), such as NiTi based alloys, is a very interesting and relevant topic for several industrial applications in the biomedical, sensor and actuator fields. Laser technology is one of the most suitable methods for the manufacturing of products in the aforementioned fields, mainly when small and precise features have to be included. Due to the thermal nature of this process, study of its effect on the functional properties of these materials is needed. Except for binary NiTi, few results on the laser machining of NiTi based alloys are available in the literature. In this work, thin sheets of Ni40Ti50Cu10 (at.%) were processed by a fibre laser and the effect of process speed on the material properties was analysed. Scanning electronic microscopy was adopted for observation of the laser cut edges’ morphology. Chemical composition of the processed material was evaluated by energy dispersion spectroscopy and nanohardness measurements were used to estimate the heat affected zone. SMA functional properties were studied on both base and laser machined material. These characteristics are affected by laser machining for the presence of melted material; this effect can be minimised by increasing the laser process speed.     

Overcoming Microenvironment-Mediated Chemoprotection through Stromal Galectin-3 Inhibition in Acute Lymphoblastic Leukemia

Environmentally-mediated drug resistance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) significantly contributes to relapse. Stromal cells in the bone marrow environment protect leukemia cells by secretion of chemokines as cues for BCP-ALL migration towards, and adhesion to, stroma. Stromal cells and BCP-ALL cells communicate through stromal galectin-3. Here, we investigated the significance of stromal galectin-3 to BCP-ALL cells. We used CRISPR/Cas9 genome editing to ablate galectin-3 in stromal cells and found that galectin-3 is dispensable for steady-state BCP-ALL proliferation and viability. However, efficient leukemia migration and adhesion to stromal cells are significantly dependent on stromal galectin-3. Importantly, the loss of stromal galectin-3 production sensitized BCP-ALL cells to conventional chemotherapy. We therefore tested novel carbohydrate-based small molecule compounds (Cpd14 and Cpd17) with high specificity for galectin-3. Consistent with results obtained using galectin-3-knockout stromal cells, treatment of stromal-BCP-ALL co-cultures inhibited BCP-ALL migration and adhesion. Moreover, these compounds induced anti-leukemic responses in BCP-ALL cells, including a dose-dependent reduction of viability and proliferation, the induction of apoptosis and, importantly, the inhibition of drug resistance. Collectively, these findings indicate galectin-3 regulates BCP-ALL cell responses to chemotherapy through the interactions between leukemia cells and the stroma, and show that a combination of galectin-3 inhibition with conventional drugs can sensitize the leukemia cells to chemotherapy.     

Kinetic analysis of cellular internalization and expulsion of unstructured D-chirality cell penetrating peptides

Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of a D-chirality CPP as bio-vector in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics.     

Visceral Adipose Tissue Displays Unique Metabolomic Fingerprints in Obesity,Pre-Diabetes and Type 2 Diabetes

Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (¹H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.     

Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.     

Screening of 42 Bacillus isolates for ability to ferment soybeans into dawadawa

Forty-two cultures of Bacillus species isolated from soybean dawadawa were screened for their proteolytic activity on Skim Milk Agar, amylolytic activity on Starch Agar, and ability to grow on Soybean Agar. Distinct differences were observed between the cultures for all the criteria. Eleven isolates were selected for laboratory fermentation trials and each produced soybean dawadawa which was found acceptable by a taste panel. The pH of the samples, which increased from 6.37-6.58 to 8.22-8.85 during fermentation, were significantly different at P< or =0.05 for the different cultures. In the fermented samples, Bacillus counts exceeded 10(9) cfu/g, with the population of only one sample being significantly different at P< or =0.05. A market focus group familiar with soybean dawadawa selected Bacillus subtilis 24BP(2) and B. subtilis FpdP(2) as the best potential starter cultures. A taste panel found no significant differences in overall acceptance between soybean dawadawa either fermented spontaneously or with B. subtilis 24BP(2) and also between soybean dawadawa fermented with either B. subtilis 24BP(2) or B. subtilis FpdP(2).     

Effect of Chemisorption and Physisorption of Water on the Surface Structure and Stability of alpha-Alumina

Chemisorption and physisorption of water onto the {0001}, {1011}, {1120}, and {2243} surfaces of alpha-alumina have been studied via atomistic simulation techniques, using potentials that have been verified against the structures of hydrated ß-alumina and diaspore. Both physisorption and chemisorption of all surfaces are energetically favorable, especially the hydroxylation of dipolar oxygen-terminated planes. The equilibrium morphology is calculated, as a way to assess the change in surface energies, and the equilibrium morphologies agree with the experimentally observed crystal morphologies. The calculated energies of both physisorption and chemisorption agree well with experimentally obtained hydration energies.     

Modeling contextual security policies

As computer infrastructures become more complex, security models must provide means to handle more flexible and dynamic requirements. In the Organization Based Access Control (OrBAC) model, it is possible to express such requirements using the notion of context. In OrBAC, each security rule (permission, prohibition, obligation or dispensation) only applies in a given context. A context is viewed as an extra condition that must be satisfied to activate a given security rule. In this paper, we present a taxonomy of different types of context and investigate the data the information system must manage in order to deal with these different contexts. We then explain how to model and evaluate them in the OrBAC model.